Although smoking remains the leading cause of death and disability in the U.S., data addressing anxiety-related individual difference variables among smokers that may relate to increased risk for developing panic disorder and the maintenance of smoking behavior are highly limited. The absence of such information seriously hinders efforts to identify smokers with increased susceptibility to panic-related problems and stymies the future development of specialized prevention programs that can meaningfully address their unique needs. The present revised R03 proposal should help begin to fill these important gaps in the literature by examining the extent to which anxiety sensitivity may moderate (1) the relation between level of smoking and fear responding to bodily sensations and (2) the relation between negative affect reduction expectancies and level of smoking. We will examine 110 nonclinical individuals who are current smokers (between 5 and 40 or more cigarettes per day, with the average smoking level for the total sample being 20 cigarettes per day) using a CO2 challenge procedure. Subjects will complete a diagnostic interview to rule out psychopathology (excluding nicotine dependence), expired Carbon Monoxide (CO) and salvia cotinine analyses as well as a set of self-report measures assessing psychological and smoking characteristics. After a 15-minute break during which they will then smoke a standardized cigarette (to equate nicotine withdrawal), they will complete the CO2 challenge. The session will last approximately 2.5 hours. The results of this project will provide the critical knowledge and requisite information to assist in future efforts to develop specialized prevention programs for panic disorder that specifically target the malleable risk factors of cigarette smoking and anxiety sensitivity. Thus, the present proposal is innovative in the sense that it is aimed at developing empirical knowledge about a unique group of high-risk individuals, for whom no specialized prevention approach to address their specific needs currently exists or is in development. This research also will uniquely contribute to our theoretical understanding of the co-morbidity of anxiety psychopathology and substance use disorders generally and aid in better understanding moderator models of smoking's effects on negative emotional responding specifically.